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Infusions of a so-called broadly neutralizing antibody (bNAb) against HIV were safe and suppressed the virus briefly when anti-retroviral medications were stopped, but HIV rebounded within weeks in two small phase I clinical trials.

Note that prior experience with anti-retroviral medications and these phase I studies suggest that antibody-based HIV suppression will probably require multiple bNAbs that target different sites on the HIV envelope glycoprotein.

Infusions of an antibody against HIV were safe and appeared to suppress the virus briefly when anti-retroviral medications were stopped, researchers said.

But in two small phase I clinical trials, HIV rebounded within weeks of stopping standard triple-drug therapy, according to Tae-Wook Chun, PhD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., and colleagues.

VRC01 is a so-called broadly neutralizing antibody (bNAb) that targets a site in the HIV envelope glycoprotein; it is "broadly neutralizing" because in the lab it is effective against many different strains of HIV.

Nearly 90 such molecules are now known, but VRC01 is one of the first to be made in large enough quantities to be tested in clinical trials.

The current finding is reminiscent of the early attempts to treat HIV with the nucleoside reverse transcriptase inhibitor zidovudine (AZT) used as a single agent, Chun and colleagues noted.

In those early studies, an initial drop in plasma levels of HIV RNA was inevitably followed by viral rebound and the development of HIV mutants with resistance to zidovudine.

It was only with the advent of triple-drug therapy with anti-retroviral medications (ARVs) attacking different aspects of HIV replication that it became possible to establish reliable suppression and overcome the ability of HIV to develop resistance.

Similarly, Chun and colleagues concluded, the studies suggest that antibody-based HIV suppression will "probably require multiple bNAbs that target different sites on the HIV envelope glycoprotein."

The conclusion is both reasonable and not surprising, commented Mitchell Warren, executive director of the New York-based HIV advocacy group AVAC.

Warren told MedPage Today that the "recognition that [broadly neutralizing antibodies] target different points of the virus makes the analogy to ARV development quite apt."

He added that VRC01 is a first-generation antibody. "Work with it now is laying the groundwork for many prevention and therapeutic approaches that will be studied in the years to come."

The two trials had similar designs, Chun and colleagues reported.

In both, participants were on successful HIV therapy with robust immune systems and no detectable virus in their plasma. They were given an infusion of VRC01 at the start of each trial and then stopped taking their ARVs.

More infusions of VRC01 followed, at different schedules in each trial, and participants continued to get the antibody until the virus rebounded to more than 200 copies of HIV RNA per milliliter of plasma.

The goals of the trials -- one run by the NIH and one by the AIDS Clinical Trials Group (ACTG) -- were to examine the safety, side effects, pharmacokinetics, and antiviral activity of VRC01.

The safety and side-effects profiles were good, the researchers noted. All participants completed their infusion schedules as planned, and there were no adverse events considered to be related to VRC01.

One serious adverse event did occur in the trial -- a participant was briefly admitted to hospital to recover from conscious sedation following endoscopy to evaluate possible hematemesis after alcohol ingestion, Chun and colleagues reported.

To evaluate the antiviral activity of the molecule, the researchers compared the time to viral rebound with that seen in historical controls from earlier analytic treatment interruptions.

Viral rebound occurred in all patients, with a median time to rebound of 4 weeks in the ACTG study and 5.6 weeks in the NIH trial.

Historically, only 13% of people maintained viral suppression 4 weeks after stopping ARVs, the researchers said.

In contrast, 38% of those in the ACTG trial and 80% of those in the NIH study were still suppressed at week 4, differences that were significant at P=0.04 and P<0.001, respectively.

But by week 8 of the trials, the difference from historical controls was no longer significant, the researchers reported.

"We are still in the early days of bNAbs," AVAC's Warren commented, but patients need more treatment options "so the possibility of bi-monthly or quarterly injections or infusions, compared to daily tablets, could be tremendously helpful."

The trials had support from the National Institute of Allergy and Infectious Diseases, the Penn Center for AIDS Research, the Penn Clinical Trials Unit, the University of Alabama at Birmingham (UAB) Center for AIDS Research, the UAB Clinical Trials Unit, the AIDS Clinical Trials Group Statistical and Data Analysis Center, and a Ruth L. Kirschstein National Research Service Award. There was no commercial support.

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